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微小RNA-93-5p通过与细胞周期蛋白D2(CCND2)的3'非翻译区(3'UTR)结合来抑制卵巢癌的恶性程度并对其进行负调控。

miR-93-5p suppresses ovarian cancer malignancy and negatively regulate CCND2 by binding to its 3'UTR region.

作者信息

Chen Guotong, Yan Yiwei, Qiu Xiaojv, Ye Chengfeng, Jiang Xingmei, Song Shuo, Zhang Yibo, Chang Huanhuan, Wang Leqi, He Xuehuan, Tang Lingrong, Zhang Qingyu, Zhang Ying

机构信息

Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Graduate School of Guangdong Medical University, Zhanjiang, China.

出版信息

Discov Oncol. 2022 Mar 20;13(1):15. doi: 10.1007/s12672-022-00478-1.

Abstract

Ovarian cancer is the most fatal gynecological cancer worldwide, yet the fundamental mechanism of malignancy acquisition in ovarian cancer remains unknown. miRNA has been implicated to a variety of diseases, including cancer initiation and progression. Cyclin-D2 (CCND2) is ubiquitously implicated in cancer uncontrol cell proliferation. Bioinformatic research revealed that CCND2 is a candidate gene for miR-93-5p with a binding site in its 3'UTR region in the current study. Using our ovarian cancer sample, we verified that miR-93-5p is negatively correlated with CCND2 mRNA and protein levels. Luciferase report assay revealed miR-93-5p inhibits CCND2 production through binding to the 3'UTR region. The expression of miR-93-5p in ovarian cancer patient samples was then determined, and a survival analysis was performed. Our findings showed that miR-93-5p is downregulated in ovarian cancer and is a favorable predictive factor in ovarian cancer patient. CCK8 assay, wound healing assay and flow cytometry-based cell cycle and apoptotic cell analyses were employed here. We found that miR-93-5p suppresses ovarian cancer cell proliferation and migration while enhances cell death. Our research certified that miR-93-5p reduces ovarian cancer malignancy by targeting CCND2.

摘要

卵巢癌是全球最致命的妇科癌症,然而卵巢癌发生恶性病变的根本机制仍不清楚。微小RNA(miRNA)与多种疾病有关,包括癌症的发生和发展。细胞周期蛋白D2(CCND2)普遍参与癌症失控的细胞增殖过程。生物信息学研究表明,在本研究中CCND2是miR-93-5p的一个候选基因,其3'非翻译区(UTR)有一个结合位点。利用我们的卵巢癌样本,我们证实miR-93-5p与CCND2的mRNA和蛋白水平呈负相关。荧光素酶报告基因检测显示,miR-93-5p通过与3'UTR区域结合抑制CCND2的产生。然后测定了卵巢癌患者样本中miR-93-5p的表达,并进行了生存分析。我们的研究结果表明,miR-93-5p在卵巢癌中表达下调,是卵巢癌患者的一个有利预测因子。这里采用了CCK8检测、伤口愈合检测以及基于流式细胞术的细胞周期和凋亡细胞分析。我们发现,miR-93-5p抑制卵巢癌细胞的增殖和迁移,同时促进细胞死亡。我们的研究证实,miR-93-5p通过靶向CCND2降低卵巢癌的恶性程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/699f/8934892/57d1f1be78fe/12672_2022_478_Fig1_HTML.jpg

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